August 2001
From Journal of Clinical Investigation
T cell responses in aplastic anemia Immunosuppressive drugs generally lead to substantially improved blood cell counts in individuals with aplastic anemia (AA), a severe decline of all blood cell lineages in which the marrow is deficient in hematopoietic cells. For this reason, although AA�s pathogenesis is obscure, it seems likely that autoimmune responses block hematopoiesis at an early stage but do not entirely eliminate early pluripotent stem cells. Here, Zeng and coworkers provide a first glimpse at some quirks of the immune system in AA patients. These authors have prepared T cells from within the marrow of 5 people with serious but treatable aplastic anemia. Cloning and DNA analysis of the T cell receptors from one of these patients shows that one sequence form of the complementarity determining region CDR3 is highly represented in patients� marrow. This form, dubbed JZ1.1, carries a specific heptapeptide sequence that is also found in the other patients studied but is absent in controls. Isolated T cells of this TCR type can suppress hematopoietic stem cell proliferation in co-culture experiments, diminishing the growth of myeloid and erythroid cell precursors alike. Interestingly, these JZ1.1 T cells appear to be specific for autologous stem cells derived from the patient at a time of severe disease� marrow cells derived from a healthy, MHC-matched control donor, or even from the patient after successful treatment, are not killed by exposure to JZ1.1 cells. Hence, it appears that T cells of this type are activated to respond to some still-unknown determinant that is present on early hematopoietic stem cells during periods of acute disease.
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